People living with human immunodeficiency virus (PLHIV) are living longer because of increased access to effective medications that slow disease progression. As PLHIV age, they are at an increased risk for developing cardiovascular disease (CVD), and for the past 20 years,1 the global burden of human immunodeficiency virus (HIV)–associated CVD has tripled. Cardiorespiratory fitness (CRF) is one of the best indicators of CVD-related morbidity and mortality among PLHIV, yet CRF is low. A recent systematic review and meta-analysis of 24 studies reported that PLHIV have among the lowest levels of CRF (26.4 mL/min per kilogram) of any population living with a chronic illness.2
Increasing the amount and intensity of physical activity is one of the best strategies to improve CRF. Data from recent clinical trials suggest that physical activity can also improve CRF in PLHIV,3,4 but physical activity among PLHIV in the community remains low.5 Furthermore, physical activity varies by sex and age in both PLHIV5 and general populations, yet how the relationship between physical activity and CRF in PLHIV is moderated by sex and age is not well described. Cardiorespiratory fitness reflects one's ability to transport inhaled oxygen to the muscles, enabling him or her to perform physical work. Untangling these relationships in a large, multisite, heterogeneous population can help to better identify potential intervention strategies to improve physical activity in PLHIV globally. Our study purposes were to describe physical activity and CRF by sex and age and examine the association between physical activity and CRF in a diverse sample of PLHIV.
Researchers from the International Nursing Network for HIV Research conducted a multisite cross-sectional study to describe physical activity and CRF by sex and age as well as the association between physical activity and CRF in PLHIV.6 As a skilled research network, each site contained significant infrastructure to facilitate participant recruitment. This infrastructure included local institutional review board (IRB)–approved research registries maintained by the sites and collaborative relationships with local clinical providers, community centers, and AIDS Service Organizations.6 Consistent with this network's procedural framework, the coordinating site finalized the study protocol, developed the standardized training modules, and obtained the primary IRB approval from University Hospitals Cleveland Medical Center. All site principal investigators provided input to enhance the final study design, were trained and certified in all study procedures, and obtained local IRB approval before data collection.
Sample and Recruitment
To be eligible for study participation, individuals had to be 18 years or older and have a confirmed positive HIV laboratory test (HIV+ enzyme-linked immunosorbent assay with confirmatory polymerase chain reaction or Western blot). Those who had a medical contraindication for exercise as determined by the American Heart Association criteria,7 were not able to be physically active without an assistive device (ie, cane, walker, wheelchair), or were not able to communicate in English or Spanish were excluded.
Participants were recruited either via telephone or in person using locally approved IRB procedures, responding to study advertisements in relevant venues (eg, clinic waiting rooms, AIDS service organizations). If interested, a research assistant screened potential participants with an IRB-approved script to describe the study purpose and determine whether candidates met eligibility criteria. All sites completed a common screening form that tracked recruitment method, number of potential participants contacted, and number of and reason for those who screened out of the study. Those who were eligible for the study were given informed consent documents to review, including a consent for the study team to access to his or her medical records, and were scheduled for a data collection visit.
Because of the cross-sectional nature of the study, and to help account for the potential confounding effects of weather-related changes in different seasons,8 we planned to recruit and enroll an evenly distributed number of participants across seasons. Each site attempted to enroll approximately 25% of the total anticipated sample in each quarter of the calendar year.
Trained study staff met with eligible participants and reviewed an informed consent document that described the study's purpose, procedures, risks, and potential benefits. After confirming understanding, the staff member obtained written informed consent and was available to assist participants to complete the measures. Study staff collected anthropometric assessments and the 6-minute walk test (6MWT) to measure CRF. All data were entered in a central Research Electronic Data Capture (RedCAP) database housed at the coordinating site, where it was cleaned and checked for quality regularly. Upon completion of the procedures, participants received an incentive amount consistent with local standards (USD $5–$50). All study procedures for this analysis occurred between January 2016 and September 2017.
Our primary predictor variables were age, sex, and physical activity. Our primary outcome was CRF as measured by the 6MWT. Demographic, clinical, and anthropomorphic variables were collected either to describe the sample or to examine as potential effect modifiers.
Demographic, Clinical, and Anthropometric Characteristics
All participants completed self-reported sociodemographic items; medical chart abstraction identified the number of years a participant had been living with HIV, current CD4+ T-cell count, current HIV viral load, and current and past comorbid conditions. Participants' standardized height, weight, and waist and hip circumference measures (in triplicate, to the nearest centimeters) were measured by the study staff.
Participants' physical activity in the past week was assessed using the 7-day Physical Activity Recall (PAR). The 7-day PAR is a semistructured interview that estimates an individual's time spent in light, moderate, and vigorous physical activity for the 7 days before the interview (Table 1).12 Its validity and reliability have been repeatedly evaluated in diverse samples for the past 20 years, and its psychometric properties are sound.13 It has been correlated with the criterion standard, objective measure of accelerometer (ρ = 0.50–0.54, P < .001).14 The standardized interview format was as follows: An interviewer explains (eg, defines) light, moderate, and vigorous physical activity to the participant and asks the participant to recall activities for the past 7 days. The interviewer guided each participant through the recall process, day by day, to determine duration and intensity of the physical activities. We used REDCap's calculation feature to total the time spent doing light, moderate, and vigorous physical activities in the past 7 days.
Cardiorespiratory fitness was measured with the widely used and validated 6MWT.15,16 We conducted the 6MWT according to American Thoracic Society guidelines.17 Before each test, participants remained seated for 10 minutes. After this rest period, we obtained the participant's blood pressure, heart rate, dyspnea, and overall fatigue using the Borg scale. After that, participants were instructed to walk as far as possible for 6 minutes, back and forth in a 30-m–long premeasured course on a flat surface, with the distance marked using cones. Participants were instructed to not run or jog during the walk test. Standard phrases of encouragement were given during the test. After each test, heart rate, Borg dyspnea, and fatigue levels as well as guides marking the distance covered were recorded by the research assistant. The total distance walked was rounded to the nearest meter. We recently validated this submaximal measure against maximal CRF tests in PLHIV and found it was associated with VO2 peak.18 We calculated sex- and age-predicted distance using the Ross et al19 (2010) validated equation to estimate VO2 peak from total distance achieved on the 6MWT (VO2 peak [mL/kg per minute] = 4.948 + 0.023 × 6 MWD [meters]). We used REDCap's calculation feature to ensure accurate conversion of participant weights (kilograms) and 6MWT distances (meters) collected across sites. The calculation yielded a value that can be interpreted as participants' VO2 peak.19
Data were cleaned before any analyses, and distributional assumptions for the outcome variables were checked before studying relationships among our variables of interest. We checked all variable distributions (Table 1) by running frequency analyses, univariate statistics, and inspecting graphs. Categorical variables were summarized using frequencies and percentages. Continuous variables, depending on their distribution, were summarized using either mean values and standard deviations or medians and interquartile ranges.
We used analysis of covariance to examine the physical activity and CRF patterns by sex and age. Consistent with previous work describing CRF in large samples,20,21 we categorized age by decade to examine these patterns over time. To assess the association between physical activity and sex, we conducted 2 multiple linear regressions. In addition to this primary relationship, we examined the independent effects of age, employment status, HIV viral load, and season enrolled by adding these covariates to the models. All statistical analyses were performed using STATA version 14.0 (College Station, Texas), and P values less than .05 were considered statistically significant.
We screened 741 adult PLHIV, of which 4 did not meet eligibility criteria. Of the 737 who did meet criteria, 35 were lost to follow-up. We enrolled 702 adult PLHIV at 6 diverse sites across the United States (Cleveland, Ohio; Newark, New Jersey; New York City, New York; Norfolk, Virginia; Corpus Christi, Texas; and San Francisco, California) and in Bangkok, Thailand. Participants' average age was 50.5 (±11.1) years; most were male (61%), disabled or unemployed (54%), and permanently housed (77%). On average, participants had been living with HIV for approximately 14 (±9.35) years, were prescribed HIV medications (92%) and virally suppressed (78%), and had at least 1 physical comorbidity (61%).
Participants reported engaging in a median of 85 minutes of light physical activity and 30 minutes of moderate physical activity in the past 7 days. However, men reported engaging in more light and moderate physical activity compared with women (all Ps < .05). Participants walked an average of 402 (±104) m on the 6MWT, with expected differences by sex. However, both men and women achieved similar rates (68% vs 69%, P = .96) of their sex- and age-predicted distance on the 6MWT. Additional demographic and medical characteristics of the sample can be found in Table 2.
Table 3 displays the physical activity and CRF characteristics of our sample by sex and age. The amount of physical activity participants engaged in did not vary significantly by decade, nor did the number of participants engaging in any physical activity (all Ps > .05). However, the ability to achieve the age- and sex-predicted distance on the 6MWT improved as ages increased among both men and women (P < .001). This relationship persisted even after controlling for employment status, season, and physical activity (Table 4).
Finally, in examining the association of physical activity to CRF, we observed that, for women engaging in any vigorous physical activity in the past week, there was a 7.31% increase in achieving their age- and sex-predicted distanced on the 6MWT (P < .001). After controlling for known covariates, we did not observe a similar relationship in men (P > .05). Full multiple regression models can be found in Table 4.
The authors of this large, multisite study confirmed that, among PLHIV engaged in HIV care, self-reported physical activity is markedly low. Similar findings have been reported in other clinic-based cohorts: CNICS (n = 5370) and the Women's Interagency HIV Study (n = 178) research cohorts.5,22 Internationally, the Dutch AGEhIV cohort also found that PLHIV engaged in less physical activity compared with HIV-negative participants (44.3% vs 53%, P = .005),23 as did the Swiss HIV Cohort Study.24 Taken together, the authors of these studies suggest that PLHIV across settings engage in low levels of physical activity and interventions to improve the amount of physical activity in PLHIV are needed. However, these data conflict with VanCampfort et al's25 (2018) meta-analysis of physical activity among PLHIV, which found that, on average, PLHIV engaged in 92.4 minutes of physical activity per day. This discrepancy may be explained by the small number (n = 144) of pooled participants in that meta-analysis.
In addition to low amounts of physical activity reported, PLHIV in our study engaged in very little vigorous physical activity. Yet, among women living with HIV, engaging in any vigorous physical activity was the only physical activity intensity associated with improved CRF. Moderate to vigorous physical activity has been shown to reduce mortality among adults 50–79 years old in the National Health and Nutrition Examination Survey observational cohort.26 However, an additional National Health and Nutrition Examination Survey analysis suggested that this relationship was dose dependent and varied based on participants' baseline physical activity level.27 In other words, sedentary adults may benefit from light or moderate physical activity, compared with highly active adults who only experience a mortality benefit from vigorous activity. These data highlight how little is known about how physical activity duration, frequency, and intensity impact CRF and cardiovascular health in PLHIV, specifically in women who have increased rates of CVD compared with women not living with HIV.28 Yet, they also suggest that there is a clear need to evaluate baseline activity levels in PLHIV and that physical activity interventions targeted to this population should carefully consider how to assist this population to engage in higher-intensity physical activity. Furthermore, these data demonstrate that age and sex are potential tailoring factors. Our finding that women derive the most cardiorespiratory benefits from higher-intensity physical activity is novel and, if replicated, could help us understand how to address their elevated cardiovascular risk.29 A potential explanation for this finding is that women with HIV, particularly those who are postmenopausal,29 may have too many cardiovascular risk factors for traditional exercise strategies to work and they may need boosted strategies such as high-intensity interval training to help overcome this heightened risk.
One of the most intriguing findings from this study was that, as PLHIV aged, there was a significant increase in their ability to achieve their sex- and age-predicted 6MWT distance. Specifically, we observed that, starting in their fifth decade, ~70% of PLHIV achieved their age- and sex-predicted 6MWT distance, compared with 63% of those in their third or fourth decade. If replicated, there are several possible explanations for this finding. The care of PLHIV across the life span and around the world requires frequent contact with the healthcare team to obtain routine laboratory values, prescribe and dispense HIV antiretroviral medications, and follow up for side effects.30 Through various mechanisms (eg, increased diagnosis and treatment), this increased contact may improve their CRF, reducing other comorbidities such as respiratory disease and CVD. An important implication of this finding is that, as this older group of PLHIV has survived a once-fatal disease and have become more engaged in their healthcare, they may be more amendable to interventions to improve higher-intensity physical activity interventions compared with younger PLHIV. Messages conveyed to PLHIV at routine healthcare appointments should emphasize how all physical activities can lead to healthy aging with HIV and highlight the potential importance and safety of high-intensity or vigorous physical activity.31 However, more research is needed to understand the effect of various physical activity intensities on physical functioning, symptom experience, and cardiovascular health to design precise, effective physical activity interventions for PLHIV across the life span.3,32
Our study yielded additional data reinforcing the low levels and intensities of physical activity of PLHIV in the United States and in Thailand and novel data describing unique relationships between physical activity and sex and CRF by age. These findings are bolstered by our large, diverse, multisite cohort of PLHIV and purposive sampling by season, yet there are limitations that must be considered. Most importantly, our measure of physical activity was self-reported. Although the 7-day PAR was validated against objective measures of physical activity (ie, accelerometer),14 it still relies on individual participant recall and may overestimate or underestimate activity. Similarly, we used the 6MWT, not maximal cardiorespiratory stress testing, to estimate VO2 peak. These measures were chosen because some of our sites had limited resources and would not have been able to use more robust testing measures. By selecting assessments that are less resource intensive, we were able to describe important relationships for this growing population. Future work should carefully consider how to include these criterion standard measures in large, diverse, global HIV cohorts. In addition, our sample predominately includes PLHIV who are in routine HIV care, and our findings, particularly the relationship between age and ability to achieve sex- and age-predicted 6MWT distance, may not be generalizable to those who are not engaged in HIV care.
A large, diverse sample of PLHIV engages in low amounts of physical activity, yet among women living with HIV, engaging in vigorous physical activity was associated with improved CRF. The authors of this study suggest that, although we clearly need more effective interventions to improve physical activity amount and intensity, we also need more evidence on how to tailor those interventions, the clinical and mechanistic effects of various types of physical activity on the cardiovascular health of PLHIV, and the role of sex and age in modifying these relationships. Future work should consider these important factors to develop effective, sustainable, and cost-effective physical activity interventions.
What's New and Important
- People living with HIV engage in low levels of physical activity, and new strategies to improve both the amount and intensity of physical activity are needed.
- Physical activity is associated with improved CRF in women, but this relationship was not found in men.
- Physical activity interventions for PLHIV may need to be tailored by sex to address unique biological factors affecting cardiovascular health.
The authors thank the many men and women living with HIV who participated in this study and the contributions of Christine Horvat Davey, Jackson Currie, and Saint Louis College, Bangkok, Thailand.
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Keywords:Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved
cardiovascular disease; cardiovascular fitness; HIV; physical activity